Orexins, a novel family of hypothalamic neuropeptides, modulate pituitary luteinizing hormone secretion in an ovarian steroid-dependent manner.

Orexin A and orexin B are a newly described family of orexigenic hypothalamic neuropeptides. The distribution of orexin immunoreactive fibers overlaps with the luteinizing hormone-releasing hormone (LHRH) neuronal system in the septo-preoptic area and the arcuate nucleus-median eminence region. To test the hypothesis that orexins may be involved in the regulation of pituitary LH secretion by influencing LHRH release, the effects of orexin A and orexin B on LH secretion were evaluated in ovariectomized (ovx) and ovarian steroid-treated ovx rats. Intracerebroventricular injection of orexin A or orexin B rapidly stimulated LH secretion in a dose- (0.3 and 3.0 nmol) and time-related fashion in estradiol benzoate- (EB) and progesterone (P)-pretreated ovx rats. Peak plasma LH concentration at 10 min were significantly higher in orexin A- than in orexin B-injected rats. On the other hand, both orexins (3 nmol) inhibited LH release in unprimed ovx rats. This ovarian steroid-dependent bimodal LH response is reminiscent of that of other orexigenic neuropeptides, such as neuropeptide Y. These findings show that orexins belong to a group of hypothalamic messengers that neurochemically bridge the regulatory networks that controls reproduction and energy balance.